Cancer is a leading cause of death worldwide and US. It is estimated that 1 in 4 deaths in US is due to cancer. Current cancer therapies target every aspect of cancer cell growth and division except translation of RNA into protein by the ribosome. Increased ribosome activity and protein translation however, is a hallmark of cancer cells and is required for disease progression.
The ribosome is not typically a target for cancer therapy. While ribosome activity and protein translation can be regulated by blocking the elongation step of translation at the ribososome using “anti-ribosomals,” these anti-ribosomals have been omitted from cancer therapies as a result of two strong, long-standing biases. First, translation inhibitors are thought to lack the specificity required to target cancer cells. Second, translation inhibitors are thought to be too toxic to be used as therapeutics. For example, Tobey et al. concluded that bouvardin, a translation inhibitor, “. . . does not appear to possess the type of properties normally associated with a useful chemotherapeutic agent” (Tobey et al., CANCER RESEARCH 38, 4415-4421, December 1978). Currently, there is only one FDA-approved anti-cancer agent that targets the ribosome (homoharringtonine, approved for chronic myeloid leukemia on Oct. 26, 2012). No agents approved for the treatment of solid tumors target the ribosome.
There is a need in the art to develop new cancer therapeutics which target ribosome activity and protein translation for the treatment of cancer.